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HPLC determination of histamine, serotonin, dopamine, and noradrenaline in the brain tissue of rats with portocaval anastomoses (PCA) has revealed a selective increase in histamine concentration . In the posterior hypothalamus, the steady-state level of the amine metabolites showed an inverse pattern ; N-tele-methylhistamine (t-McHA), as estimated by gas chromatography-mass spectrometry, was not changed significantly by portocaval shunting, whereas 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid were more than doubled . Interestingly, the net increase in t-MeHA concentration in response to pargyline (80 mg/kg i .p .) was almost the same for PGA and sham-operated rats . This implies that the great enhancement of the histamine level in this area might be a consequence of the persistent stimulation of its synthesis and the unchanged activity of histaminergic neurons . In the rest of the brain, on the other hand, the steadystate level of t-MeHA was higher after PCA (3 .8-fold}, as were the levels of 5-HIAA and homovanillic acid . Surprisingly, t-MeHA remained unchanged after monoamine oxidase blockade . Of the pargyline-induced alterations in the concentrations of indoles and catechols, the most pronounced were those in the serotonin level ; serotonin was elevated more than twofold in hypothalamus and more than 12-fold in the rest of the brain, with a concomitant 80% decrease in 5-HIAA . The dopamine and, to a much smaller extent, noradrenaline levels were also increased, and the levels of homovanillic acid and 3,4-dihydroxyphenylacetic acid fell below the detection limit . The study suggests that at least two different mechanisms operate in the brains of PCA rats to counteract the excessive synthesis of neuromediators, e .g ., increased deposition and increased metabolism, Key Words : Portocaval anastomosis-Histamine-Methylhistamine-Catecholamines-Serotonin . J. Neurochem . 62, 615-620 (1994) .Despite extensive studies, the mechanisms involved in hepatic encephalopathy (HE) still remain a matter of debate . One of the most striking changes 6IS resulting from portocaval anastomoss (PCA), which

Rats with portocaval anastomosis (PCA), an animal model of hepatic encephalopathy (HE), have very high brain histamine concentrations. Our previous studies based on a biochemical approach indicated histamine accumulation in the neuronal compartment. In this study, immunohistochemical evidence is presented which further supports the amine localization in histaminergic neurons. These neurons become pathological in appearance with cisternae frequently seen along histaminergic fibres in many brain areas, including the hypothalamus, amygdala, substantia nigra and cerebral cortex. Such formations were not observed in sham-operated animals. The neuronal deposition is predominant, and unique for histamine. It serves as a mechanism to counterbalance excessive brain neurotransmitter formation evoked by PCA. However, there are other mechanisms. The data provided here show that there is also a significant increase in histamine catabolism in the shunted rats, as reflected by both the higher brain N-telemethylhistamine (t-MeHA) concentration and urinary excretion of N-tele-methylimidazoleacetic acid (t-MeImAA), a major brain histamine end product. The stomach, in addition to the brain, is a site of enhanced histamine synthesis in portocavally shunted subjects. After gastrectomy or food deprivation to eliminate the contribution of the stomach, shunted rats excrete significantly more t-MeImAA, implying the role of the CNS. This last finding suggests that under strictly defined conditions, namely in parenterally fed HE patients with abnormal plasma L-histidine, the measurement of urinary t-MeImAA might provide valuable information concerning putative brain histaminergic activity.